Selective modification of sucrose presents a major synthetic challenge because of the multiplicity of reactive OH groups and the acid lability of the glycosidic linkage. When the target of interest is the commercially important non-nutritive sweetener, sucralose, i.e., 4,1', 6'-trichloro-4,1', 6'-trideoxygalactosuccrose (in the process of making the compound, the stereo configuration at the 4 position is reversed; therefore, sucralose is a galacto-sucrose), the difficulty is compounded by a need to chlorinate the less reactive 4- and 1'-positions, while leaving intact the more reactive 6-position. In spite of the numerous strategies developed to preblock the 6-position, usually by forming a sucrose-6-acylate such as sucrose-6-acetate and removing the blocking moiety as by hydrolysis after chlorination and so minimize side reactions, the crude chlorination product inevitably still contains some unwanted di-tri- and tetra-chlorinated sucroses (hereinafter, respectively referred to as Di's, Tri's and Tet's), as well as the high-boiling solvent used in the reaction and the chloride salts generated in neutralization after the chlorination step. In aggregate, these present a multi-faceted purification problem and a pivotal concern to the overall economics of sucralose manufacture. The prior art teaches various combinations of distillation liquid-liquid extraction, crystallization and/or derivatization to effect said purification. We have now discovered that adsorption technology exploiting the differing affinities of the associated components for particular solid adsorbents can be applied, in various liquid-solid designs, alone or in combination with the aforementioned processes, to offer significant operational advantages over the prior art.
The simplest form of adsorption technology is the pulse mode, wherein a single concentrated mixture is introduced onto an adsorbent column, and subsequently separated into its various components under passage of a suitable desorbent. Axial or radial flow devices may be used, depending on the pressure drop needs of the system. FIG. 1 depicts a generic separation in this mode of a mixture of components (or bands of components), A, B, and C, where affinity for the adsorbent follows an order, A&gt;B&gt;C, and t.sub.o through t.sub.n denote increasing elution time (or column length). Operationally, the take-off port may be positioned at t.sub.3 or later, if all 3 bands need resolving; or at any point along the t.sub.o to t.sub.3 continuum, if some degree of overlap is tolerated. In the latter instance, if the focus is solely to purify A and C, without concern for B, one option is to just take the early and late slices of the overlapping profile at t.sub.2 and intermix the center-cut with fresh feed; the composite recycling back to the same, or cascading forward to, a second column. In these continuous pulse modes, maximum productivity is sought by operating close to the minimum acceptable resolution and minimizing the interval between feed pulses; in effect minimizing the amount of desorbent used to that which just maintains the leading edge of one pulse from catching up with the trailing edge of the one immediately preceding.
Truly continuous operation, demanding simultaneous flow of feed, desorbent and take-off(s), is also possible. In one approach, termed continuous annular chromatography (CAC), an annular column is slowly rotated about its axis, to cause the feed and desorbent, being injected from the top, to separate into helical bands in the annulus--and be duly withdrawn through discrete ports at the bottom. Though continuous in operation, this design resembles pulse in its less than efficient use of adsorbent. An alternate mechanical arrangement, termed simulated moving bed (SMB), is greatly preferred--minimizing adsorbent and desorbent usage and maximizing take-off concentrations. It consists of a fixed-bed, comprising several serial sections or columns in a closed loop, each individually capable of receiving and relieving liquid flow. In operation, the desorbent, feed and take-off ports, held in a fixed arrangement relative to one another, ratchet forward, at a fixed time interval (referred as the step time), in a direction cocurrent with the liquid flow--thus, simulating counter-current movement of the liquid-adsorbent contact. This design has won wide acceptance in the manufacture of a broad range of commodity chemicals, e.g., xylene, ethylbenzene, high fructose corn syrup and sugar, with commercial units operating up to 22 ft. in diameter. Yet another mode, termed continuous cocurrent SMB, has also been described continuously cascading the overlap fractions through a plurality of columns, utilizing an SMB-type valve-switching arrangement.
It will be understood from the above discussion that in order to apply any or all of these adsorption techniques to a particular service, one first has to discover an adsorbent-desorbent pair capable of effecting the requisite separation, and that the single-pulse mode, stripped of the mechanical complexity of the more continuous approaches, provides the intrinsic picture of the relative separation factors involved. This picture, or chromatogram, records the concentrations of each constituent in individual fractions, collected along a volumetric line, denoting desorbent flow. By convention, where the elution order directly reflects the increasing polarity of the components, the profile is termed "normal phase". This arises when a polar adsorbent is combined with a non-polar desorbent, e.g., cyclohexane on silica-gel. In contrast, the term "reversed phase" describes the pairing of an apolar adsorbent with a polar desorbent--and an elution order of decreasing polarity.
A broad diversity of application is possible--both in regard to the position and composition of the actual stream being treated. In cases, where the adsorption step can be situated in benign aqueous environments, organic resins are permitted. When the environment contains a harsh organic solvent, one is constrained to the more inert adsorbents, e.g., molecular sieves, silica-gel, zeolites, and activated carbon. We have now found that both classes of adsorbent, when combined with appropriate desorbents, can be utilized in systems applicable to a wide range of sucralose purification services.